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长链非编码 RNA FENDRR 的表达与肿瘤免疫原性相关。

LncRNA FENDRR Expression Correlates with Tumor Immunogenicity.

机构信息

College of Veterinary Medicine, Physiological Sciences, Oklahoma State University, Stillwater, OK 74074, USA.

出版信息

Genes (Basel). 2021 Jun 10;12(6):897. doi: 10.3390/genes12060897.

Abstract

FENDRR (Fetal-lethal non-coding developmental regulatory RNA, LncRNA FOXF1-AS1) is a recently identified tumor suppressor long non-coding (LncRNA) RNA, and its expression has been linked with epigenetic modulation of the target genes involved in tumor immunity. In this study, we aimed to understand the role of FENDRR in predicting immune-responsiveness and the inflammatory tumor environment. Briefly, FENDRR expression and its relationship to immune activation signals were assessed in murine cell lines. Data suggested that tumor cells (e.g., C26 colon, 4T1 breast) that typically upregulate immune activation genes and the MHC class I molecule exhibited high FENDRR expression levels. Conversely, tumor cells with a generalized downregulation of immune-related gene expression (e.g., B16F10 melanoma) demonstrated low to undetectable FENDRR levels. Mechanistically, the modulation of FENDRR expression enhanced the inflammatory and WNT signaling pathways in tumors. Our early data suggest that FENDRR can play an important role in the development of immune-relevant phenotypes in tumors, and thereby improve cancer immunotherapy.

摘要

FENDRR(胎致死性非编码发育调控 RNA,LncRNA FOXF1-AS1)是一种最近发现的肿瘤抑制长非编码(LncRNA)RNA,其表达与肿瘤免疫中涉及的靶基因的表观遗传调节有关。在这项研究中,我们旨在了解 FENDRR 在预测免疫反应性和炎症肿瘤环境中的作用。简而言之,评估了 FENDRR 在小鼠细胞系中的表达及其与免疫激活信号的关系。数据表明,通常上调免疫激活基因和 MHC I 类分子的肿瘤细胞(例如 C26 结肠、4T1 乳腺)表现出高 FENDRR 表达水平。相反,具有普遍下调免疫相关基因表达的肿瘤细胞(例如 B16F10 黑色素瘤)表现出低至无法检测到的 FENDRR 水平。从机制上讲,FENDRR 表达的调节增强了肿瘤中的炎症和 WNT 信号通路。我们的初步数据表明,FENDRR 可以在肿瘤中免疫相关表型的发展中发挥重要作用,从而改善癌症免疫治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd6f/8226633/71be46fe5096/genes-12-00897-g001.jpg

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